The generation of pluripotent stem cells that are genetically identical to an individual provides unique opportunities for basic research and for potential immunologically-compatible novel cell-based therapies (Byrne J A. (2008) Human Mol. Gen. 17:R37-41). Methods to reprogram primate somatic cells to a pluripotent state include somatic cell nuclear transfer (Stojkovic M, et al. (2005) Reprod Biomed Online 11:226-231; Byrne J A, et al. (2007) Nature 450:497-502), somatic cell fusion with pluripotent stem cells (Cowan C A, et al. (2005) Science 309:1369-1373) and direct reprogramming to produce induced pluripotent stem cells (iPS cells) (Takahashi K, et al. (2007) Cell 131:861-872; Park I H, et al. (2008) Nature 451:141-146; Yu J, et al. (2007) Science 318:1917-1920; Kim D, et al. (2009) Cell Stem Cell 4:472-476; Soldner F, et al. (2009) Cell. 136:964-977; Huangfu D, et al. (2008) Nature Biotechnology 26:1269-1275; Li W, et al. (2009) Cell Stem Cell 4:16-19). These methodologies, however, are characterized by a low reprogramming efficiency and a lack of knowledge regarding the underlying mechanisms. While it has been demonstrated previously that more differentiated cells demonstrate a lower reprogramming efficiency (Gurdon J B and Byrne J A.(2003) Proc Natl Acad Sci U S A 100:8048-8052) and different somatic cell types possess differential reprogramming ability (Aoi T, et al.(2008) Science 321:699-702; Aasen T, et al. (2008) Nature Biotechnology 2008; 26(11):1276-1284) the art has not identified a subpopulation of cells within a somatic cell type possessing differential reprogramming potential.
Isolation of a subpopulation or subpopulations of cells within a somatic cell population possessing differential reprogramming potential would provide a method to significantly increase the efficiency of reprogramming, thereby enhancing the feasibility of the potential applications based on this technology (Byrne J A. (2008) Human Mol. Gen. 17:R37-41). Isolation of such subpopulations would also provide a tool for basic research studies to understand the underlying reprogramming mechanisms.